Autonomous Shaping of the piRNA Sequence Repertoire by Competition between Adjacent Ping-Pong Sites

SUMMARYPIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements (TEs). In many species, piRNAs are generated via a complex process known as the ping-pong pathway, which couples TE cleavage with new piRNA amplification. However, the biological significance of this complexity and its impact on the piRNA sequence repertoire remain unclear. Here, we systematically compared piRNA production patterns in two closely related silkworm cell lines and found significant changes in their piRNA sequence repertoire. Importantly, the changeability of this repertoire showed a strong negative correlation with the efficiency of piRNA biogenesis. This can be explained by competition between adjacent ping-pong sites, as supported by our mathematical modeling. Moreover, this competition can rationalize how piRNAs autonomously avoid deleterious mismatches to target TEs. These findings unveil the intrinsic plasticity and adaptability of the piRNA system to combat diverse TE sequences and highlight the universal power of competition and self-amplification to drive autonomous optimization.